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CRISPR/Cas9-mediated Targeted Integration In Vivo Using a Homology-mediated End Joining-based Strategy
Published on: March 12, 2018
Cancer-specific chemotherapeutic strategy based on the vitamin K3 mediated ROS regenerative feedback and visualized
Gang-Gang Yang1, Hang Zhang1, Dong-Yang Zhang1
1MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, PR China.
Abstract:
A promising theranostic nanosystem VK3-CPT@Ru-CD is designed and fabricated by the host-guest driven self-assembly between the fluorescent adamantine-functionalized Ru(II) complexes and the ROS-labile-cyclodextrin modified thioketal linkers, in which anticancer drug camptothecin (CPT) and vitamin K3 (VK3) are effectively co-encapsulated. On account of the generative feedback between the intracellular redox cycling of VK3 and the high degree of ROS-triggered collapse of nanoparticles, VK3-CPT@Ru-CD can facilitate cancer-specific ROS amplification and drug release selectively in cancer cells, thus realizing the selective killing of tumor with minimal side-effects both in vitro and in vivo, the therapeutic effect of which is more prominent than the free anti-cancer drugs. More interestingly, the menadione structure of encapsulated VK3 can effectively quench the inherent fluorescence of Ru-CD, and a fluorescence lightening up phenomenon is observed accompanied with the ROS-triggered drug release, which can be utilized for real-time tracking of drug release in vitro and in vivo.
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